The primary effort within the past year has centered on using novel genetic approaches to understand the basis of Alzheimer's disease. We have used high density SNP genotyping in an attempt to identify regions that may contain recessive mutations or risk factors causing or contributing to disease. This has involved analysis of individual families in addition to work on larger cohorts. In addition we have contributed toward the most recently published genome wide association study in Alzheimer's disease that describes CLU and PICALM variants as significant risk loci for Alzheimer's disease. Following this finding much of our work has centered on characterizing the extent of genetic variability at the CLU and PICALM loci, across different Alzheimer's disease populations.